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Angiotensinogen (Serpin A8) [Cleaved into: Angiotensin-1 (Angiotensin 1-10) (Angiotensin I) (Ang I); Angiotensin-2 (Angiotensin 1-8) (Angiotensin II) (Ang II); Angiotensin-3 (Angiotensin 2-8) (Angiotensin III) (Ang III) (Des-Asp[1]-angiotensin II); Angiotensin-4 (Angiotensin 3-8) (Angiotensin IV) (Ang IV); Angiotensin 1-9; Angiotensin 1-7; Angiotensin 1-5; Angiotensin 1-4]

 ANGT_RAT                Reviewed;         477 AA.
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
21-JUL-1986, sequence version 1.
20-DEC-2017, entry version 148.
RecName: Full=Angiotensinogen;
AltName: Full=Serpin A8;
RecName: Full=Angiotensin-1;
AltName: Full=Angiotensin 1-10;
AltName: Full=Angiotensin I;
Short=Ang I;
RecName: Full=Angiotensin-2;
AltName: Full=Angiotensin 1-8;
AltName: Full=Angiotensin II;
Short=Ang II;
RecName: Full=Angiotensin-3;
AltName: Full=Angiotensin 2-8;
AltName: Full=Angiotensin III;
Short=Ang III;
AltName: Full=Des-Asp[1]-angiotensin II;
RecName: Full=Angiotensin-4;
AltName: Full=Angiotensin 3-8;
AltName: Full=Angiotensin IV;
Short=Ang IV;
RecName: Full=Angiotensin 1-9;
RecName: Full=Angiotensin 1-7;
RecName: Full=Angiotensin 1-5;
RecName: Full=Angiotensin 1-4;
Flags: Precursor;
Name=Agt; Synonyms=Serpina8;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
PubMed=6572971; DOI=10.1073/pnas.80.8.2196;
Ohkubo H., Kageyama R., Ujihara M., Hirose T., Inayama S.,
Nakanishi S.;
"Cloning and sequence analysis of cDNA for rat angiotensinogen.";
Proc. Natl. Acad. Sci. U.S.A. 80:2196-2200(1983).
Tanaka T., Ohkubo H., Nakanishi S.;
"Common structural organization of the angiotensinogen and the alpha
1-antitrypsin genes.";
J. Biol. Chem. 259:8063-8065(1984).
TISSUE=Brain, and Kidney;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
PubMed=4344907; DOI=10.1248/cpb.20.1579;
Nakayama T., Nakajima T., Sokabe H.;
"Comparative studies on angiotensins. II. Structure of rat angiotensin
and its identification by DNS-method.";
Chem. Pharm. Bull. 20:1579-1581(1972).
PubMed=18026570; DOI=10.2119/2007-00073.Fraga-Silva;
Fraga-Silva R.A., Pinheiro S.V.B., Goncalves A.C., Alenina N.,
Bader M., Santos R.A.S.;
"The antithrombotic effect of angiotensin-(1-7) involves mas-mediated
NO release from platelets.";
Mol. Med. 14:28-35(2008).
PubMed=20927107; DOI=10.1038/nature09505;
Zhou A., Carrell R.W., Murphy M.P., Wei Z., Yan Y., Stanley P.L.,
Stein P.E., Broughton Pipkin F., Read R.J.;
"A redox switch in angiotensinogen modulates angiotensin release.";
Nature 468:108-111(2010).
-!- FUNCTION: Essential component of the renin-angiotensin system
(RAS), a potent regulator of blood pressure, body fluid and
electrolyte homeostasis. {ECO:0000250}.
-!- FUNCTION: Angiotensin-2: acts directly on vascular smooth muscle
as a potent vasoconstrictor, affects cardiac contractility and
heart rate through its action on the sympathetic nervous system,
and alters renal sodium and water absorption through its ability
to stimulate the zona glomerulosa cells of the adrenal cortex to
synthesize and secrete aldosterone. {ECO:0000250}.
-!- FUNCTION: Angiotensin-3: stimulates aldosterone release.
-!- FUNCTION: Angiotensin 1-7: is a ligand for the G-protein coupled
receptor MAS1 (By similarity). Has vasodilator and antidiuretic
effects (By similarity). Has an antithrombotic effect that
involves MAS1-mediated release of nitric oxide from platelets.
{ECO:0000250, ECO:0000269|PubMed:18026570}.
-!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
-!- PTM: In response to low blood pressure, the enzyme renin/REN
cleaves angiotensinogen to produce angiotensin-1. Angiotensin-1 is
a substrate of ACE (angiotensin converting enzyme) that removes a
dipeptide to yield the physiologically active peptide angiotensin-
2. Angiotensin-1 and angiotensin-2 can be further processed to
generate angiotensin-3, angiotensin-4 (By similarity). Angiotensin
1-9 is cleaved from angiotensin-1 by ACE2 and can be further
processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and
angiotensin 1-4. Angiotensin 1-7 has also been proposed to be
cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME
(neprilysin) (By similarity). {ECO:0000250}.
-!- PTM: The disulfide bond is labile. Angiotensinogen is present in
the circulation in a near 40:60 ratio with the oxidized disulfide-
bonded form, which preferentially interacts with receptor-bound
-!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
EMBL; L00094; AAA98779.1; -; Genomic_DNA.
EMBL; L00091; AAA98779.1; JOINED; Genomic_DNA.
EMBL; L00092; AAA98779.1; JOINED; Genomic_DNA.
EMBL; L00093; AAA98779.1; JOINED; Genomic_DNA.
EMBL; BC078741; AAH78741.1; -; mRNA.
EMBL; BC087679; AAH87679.1; -; mRNA.
PIR; A93945; ANRT.
RefSeq; NP_602308.1; NM_134432.2.
RefSeq; XP_008770819.1; XM_008772597.2.
UniGene; Rn.6319; -.
PDB; 1SMR; X-ray; 2.00 A; B/D/F/H=30-33.
PDB; 2WXZ; X-ray; 2.80 A; A/C=25-477.
PDB; 2WY1; X-ray; 3.15 A; A/B=25-477.
PDBsum; 1SMR; -.
PDBsum; 2WXZ; -.
PDBsum; 2WY1; -.
ProteinModelPortal; P01015; -.
SMR; P01015; -.
MINT; MINT-1522474; -.
STRING; 10116.ENSRNOP00000024917; -.
BindingDB; P01015; -.
MEROPS; I04.953; -.
iPTMnet; P01015; -.
PhosphoSitePlus; P01015; -.
PaxDb; P01015; -.
PRIDE; P01015; -.
Ensembl; ENSRNOT00000024917; ENSRNOP00000024917; ENSRNOG00000018445.
GeneID; 24179; -.
KEGG; rno:24179; -.
UCSC; RGD:2069; rat.
CTD; 183; -.
RGD; 2069; Agt.
eggNOG; KOG2392; Eukaryota.
eggNOG; COG4826; LUCA.
GeneTree; ENSGT00890000139531; -.
HOGENOM; HOG000033941; -.
HOVERGEN; HBG004233; -.
InParanoid; P01015; -.
KO; K09821; -.
OrthoDB; EOG091G077M; -.
PhylomeDB; P01015; -.
TreeFam; TF343201; -.
Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
Reactome; R-RNO-375276; Peptide ligand-binding receptors.
Reactome; R-RNO-416476; G alpha (q) signalling events.
Reactome; R-RNO-418594; G alpha (i) signalling events.
EvolutionaryTrace; P01015; -.
PRO; PR:P01015; -.
Proteomes; UP000002494; Chromosome 19.
Bgee; ENSRNOG00000018445; -.
Genevisible; P01015; RN.
GO; GO:0072562; C:blood microparticle; ISO:RGD.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0070062; C:extracellular exosome; ISO:RGD.
GO; GO:0005576; C:extracellular region; ISO:RGD.
GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
GO; GO:0031701; F:angiotensin receptor binding; IMP:RGD.
GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
GO; GO:0048018; F:receptor ligand activity; ISS:BHF-UCL.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
GO; GO:0031702; F:type 1 angiotensin receptor binding; IMP:RGD.
GO; GO:0031703; F:type 2 angiotensin receptor binding; IMP:RGD.
GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; ISO:RGD.
GO; GO:0007202; P:activation of phospholipase C activity; IMP:RGD.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:BHF-UCL.
GO; GO:0003051; P:angiotensin-mediated drinking behavior; IDA:RGD.
GO; GO:0001998; P:angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure; ISO:RGD.
GO; GO:0014824; P:artery smooth muscle contraction; IDA:RGD.
GO; GO:0048143; P:astrocyte activation; ISO:RGD.
GO; GO:0001568; P:blood vessel development; ISO:RGD.
GO; GO:0002035; P:brain renin-angiotensin system; ISO:RGD.
GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISO:RGD.
GO; GO:0035411; P:catenin import into nucleus; IDA:RGD.
GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IDA:RGD.
GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:RGD.
GO; GO:0007160; P:cell-matrix adhesion; ISO:RGD.
GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
GO; GO:0006883; P:cellular sodium ion homeostasis; IMP:RGD.
GO; GO:0050663; P:cytokine secretion; IDA:RGD.
GO; GO:0042756; P:drinking behavior; ISO:RGD.
GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:RGD.
GO; GO:0008065; P:establishment of blood-nerve barrier; ISO:RGD.
GO; GO:0007588; P:excretion; ISO:RGD.
GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
GO; GO:0007565; P:female pregnancy; IEP:RGD.
GO; GO:0048144; P:fibroblast proliferation; IDA:RGD.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IMP:RGD.
GO; GO:0042445; P:hormone metabolic process; ISO:RGD.
GO; GO:0001822; P:kidney development; ISO:RGD.
GO; GO:0016525; P:negative regulation of angiogenesis; IDA:RGD.
GO; GO:0030308; P:negative regulation of cell growth; IMP:RGD.
GO; GO:0008285; P:negative regulation of cell proliferation; ISO:RGD.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
GO; GO:0051387; P:negative regulation of neurotrophin TRK receptor signaling pathway; ISO:RGD.
GO; GO:0034104; P:negative regulation of tissue remodeling; IDA:RGD.
GO; GO:0001543; P:ovarian follicle rupture; ISO:RGD.
GO; GO:0030432; P:peristalsis; ISO:RGD.
GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; ISO:RGD.
GO; GO:0045777; P:positive regulation of blood pressure; IDA:RGD.
GO; GO:0097755; P:positive regulation of blood vessel diameter; IDA:RGD.
GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISO:RGD.
GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IDA:RGD.
GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:BHF-UCL.
GO; GO:0043085; P:positive regulation of catalytic activity; IMP:RGD.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:RGD.
GO; GO:0032270; P:positive regulation of cellular protein metabolic process; ISO:RGD.
GO; GO:0010873; P:positive regulation of cholesterol esterification; ISO:RGD.
GO; GO:0050715; P:positive regulation of cytokine secretion; ISO:RGD.
GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:RGD.
GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; IDA:RGD.
GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; ISO:RGD.
GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:BHF-UCL.
GO; GO:1903598; P:positive regulation of gap junction assembly; ISO:RGD.
GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
GO; GO:2001275; P:positive regulation of glucose import in response to insulin stimulus; IDA:RGD.
GO; GO:1905589; P:positive regulation of L-arginine import across plasma membrane; IDA:RGD.
GO; GO:1905010; P:positive regulation of L-lysine import across plasma membrane; IDA:RGD.
GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:RGD.
GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
GO; GO:1900020; P:positive regulation of protein kinase C activity; ISO:RGD.
GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
GO; GO:0035815; P:positive regulation of renal sodium excretion; IDA:RGD.
GO; GO:0032930; P:positive regulation of superoxide anion generation; IDA:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IDA:RGD.
GO; GO:1904707; P:positive regulation of vascular smooth muscle cell proliferation; IDA:RGD.
GO; GO:0042981; P:regulation of apoptotic process; IDA:RGD.
GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
GO; GO:0051924; P:regulation of calcium ion transport; IDA:RGD.
GO; GO:1903779; P:regulation of cardiac conduction; ISO:RGD.
GO; GO:1901201; P:regulation of extracellular matrix assembly; ISO:RGD.
GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
GO; GO:0002027; P:regulation of heart rate; IDA:RGD.
GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IMP:RGD.
GO; GO:0014061; P:regulation of norepinephrine secretion; IMP:RGD.
GO; GO:0002019; P:regulation of renal output by angiotensin; ISO:RGD.
GO; GO:0035813; P:regulation of renal sodium excretion; IDA:RGD.
GO; GO:0001991; P:regulation of systemic arterial blood pressure by circulatory renin-angiotensin; ISO:RGD.
GO; GO:0051969; P:regulation of transmission of nerve impulse; IDA:RGD.
GO; GO:0001999; P:renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure; ISO:RGD.
GO; GO:0003014; P:renal system process; ISO:RGD.
GO; GO:0002018; P:renin-angiotensin regulation of aldosterone production; IDA:RGD.
GO; GO:0009409; P:response to cold; ISO:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0014873; P:response to muscle activity involved in regulation of muscle adaptation; IMP:BHF-UCL.
GO; GO:0009651; P:response to salt stress; ISO:RGD.
GO; GO:0051145; P:smooth muscle cell differentiation; ISO:RGD.
GO; GO:0048659; P:smooth muscle cell proliferation; IDA:RGD.
GO; GO:0051403; P:stress-activated MAPK cascade; IDA:RGD.
GO; GO:0070471; P:uterine smooth muscle contraction; IDA:RGD.
GO; GO:0042310; P:vasoconstriction; IDA:RGD.
GO; GO:0042311; P:vasodilation; IDA:RGD.
InterPro; IPR000227; Angiotensinogen.
InterPro; IPR023796; Serpin_dom.
InterPro; IPR000215; Serpin_fam.
InterPro; IPR036186; Serpin_sf.
PANTHER; PTHR11461; PTHR11461; 1.
PANTHER; PTHR11461:SF13; PTHR11461:SF13; 1.
Pfam; PF00079; Serpin; 1.
SMART; SM00093; SERPIN; 1.
SUPFAM; SSF56574; SSF56574; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Direct protein sequencing;
Disulfide bond; Glycoprotein; Reference proteome; Secreted; Signal;
Vasoactive; Vasoconstrictor.
SIGNAL 1 24 {ECO:0000269|PubMed:4344907}.
CHAIN 25 477 Angiotensinogen.
PEPTIDE 25 34 Angiotensin-1.
PEPTIDE 25 33 Angiotensin 1-9.
PEPTIDE 25 32 Angiotensin-2.
PEPTIDE 25 31 Angiotensin 1-7.
PEPTIDE 25 29 Angiotensin 1-5.
PEPTIDE 25 28 Angiotensin 1-4.
PEPTIDE 26 32 Angiotensin-3.
PEPTIDE 27 32 Angiotensin-4.
CARBOHYD 295 295 N-linked (GlcNAc...) asparagine.
CARBOHYD 319 319 N-linked (GlcNAc...) asparagine.
DISULFID 42 161 {ECO:0000269|PubMed:20927107}.
TURN 33 35 {ECO:0000244|PDB:2WXZ}.
HELIX 39 43 {ECO:0000244|PDB:2WXZ}.
HELIX 72 84 {ECO:0000244|PDB:2WXZ}.
HELIX 88 115 {ECO:0000244|PDB:2WXZ}.
STRAND 120 124 {ECO:0000244|PDB:2WXZ}.
HELIX 126 138 {ECO:0000244|PDB:2WXZ}.
HELIX 142 151 {ECO:0000244|PDB:2WXZ}.
HELIX 167 181 {ECO:0000244|PDB:2WXZ}.
STRAND 193 203 {ECO:0000244|PDB:2WXZ}.
HELIX 211 216 {ECO:0000244|PDB:2WXZ}.
TURN 217 220 {ECO:0000244|PDB:2WXZ}.
STRAND 224 228 {ECO:0000244|PDB:2WXZ}.
STRAND 231 233 {ECO:0000244|PDB:2WXZ}.
HELIX 235 250 {ECO:0000244|PDB:2WXZ}.
STRAND 267 279 {ECO:0000244|PDB:2WXZ}.
STRAND 282 284 {ECO:0000244|PDB:2WY1}.
STRAND 289 294 {ECO:0000244|PDB:2WXZ}.
STRAND 297 301 {ECO:0000244|PDB:2WXZ}.
STRAND 303 315 {ECO:0000244|PDB:2WXZ}.
TURN 316 319 {ECO:0000244|PDB:2WXZ}.
STRAND 320 340 {ECO:0000244|PDB:2WXZ}.
HELIX 341 343 {ECO:0000244|PDB:2WXZ}.
HELIX 344 351 {ECO:0000244|PDB:2WXZ}.
STRAND 353 355 {ECO:0000244|PDB:2WXZ}.
STRAND 366 373 {ECO:0000244|PDB:2WXZ}.
STRAND 375 382 {ECO:0000244|PDB:2WXZ}.
HELIX 383 389 {ECO:0000244|PDB:2WXZ}.
TURN 393 396 {ECO:0000244|PDB:2WXZ}.
HELIX 403 405 {ECO:0000244|PDB:2WXZ}.
STRAND 406 408 {ECO:0000244|PDB:2WXZ}.
STRAND 416 425 {ECO:0000244|PDB:2WXZ}.
STRAND 452 458 {ECO:0000244|PDB:2WXZ}.
TURN 459 462 {ECO:0000244|PDB:2WXZ}.
STRAND 463 471 {ECO:0000244|PDB:2WXZ}.
SEQUENCE 477 AA; 51982 MW; 689051A5788D693D CRC64;

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